GnRH Analogue Therapy Research Articles

The Role of GnRH Analogues in Improving Outcome in Women Undergoing Superovulation and Intrauterine Insemination after Surgical Correction of Mild Endometriosis: A Randomized Controlled Trial.

Treatment with laparoscopic surgery, gonadotropin-releasing hormone analog (GnRHa) therapy, superovulation (SO), and intrauterine insemination (IUI) have individual benefits in improving fertility outcomes in women with endometriosis. The aim of the study was to evaluate the role of GnRHa in improving outcome in women undergoing SO and IUI after surgical correction of mild endometriosis. This was a randomized controlled trial conducted in the Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India, over a period of 2 years and 6 months. Ninety women who were diagnosed with mild endometriosis on laparoscopy using the revised American Society for Reproductive Medicine criteria were included in the study. The patients in the study group (n=45) received a single dose of 3.75 mg GnRHa subcutaneously within 48 h of the surgery, and those in the control group (n=45) did not receive GnRHa. Thereafter, patients in both arms received SO and IUI from the next menstrual cycle. Four patients in the study group and three patients in the control group were lost to follow-up before the first cycle of ovulation induction. Primary outcomes measured in our study were live birth rates and clinical pregnancy rate. Secondary outcome measures were number of follicles >18 mm, endometrial thickness, dose and days of gonadotropin stimulation. Baseline characteristics, such as age and body mass index, were comparable in both groups. The SO and IUI cycles were comparable between the two groups with regard to the secondary outcome parameters. Pregnancy rate in the first cycle was 17.1% in the study group and 19.1% in the control group (p=0.81). The overall pregnancy rate was similar in both groups (study group=21.9%, control group=23.8%; p=1). As no patient had miscarriage or any other complication during pregnancy, live birth rate was similar to the clinical pregnancy rate. Adding GnRHa for the suppression of mild endometriosis has shown no significant improvement in the surgical management of women undergoing SO and IUI.

Gonadotropin-Releasing Hormone (GnRHa) Therapy for Central Precocious Puberty (CPP): Review of Nuances in Assessment of Height, Hormonal Suppression, Psychosocial Issues, and Weight Gain, with Patient Examples.

This review suggests a central theme: that the treatment of each patient presenting with evidence consistent with central precocious puberty (CPP) needs to be individualized. This pertains to multiple factors relating to growth and growth potential, monitoring patients on treatment with gonadotropin-releasing hormone analogue (GnRHa), evaluating psychological issues with CPP and therapy, and concerns about weight gain during GnRHa therapy. Individual cases are presented. New data on adult height and rate of bone age advance are included. GnRHa treatment is effective in improving adult height in children with precocious onset of puberty, rapid progression, and good growth potential. Monitoring suppression adequacy involves a random LH level < 0.6 IU/L or a GnRHa-stimulated peak LH level < 4 IU/L as long as physical exam, growth rate, and rate of bone age progression, are also consistent with suppression. Abnormal psychosocial issues are rare with concerns primarily being related perceptions, real or perceived by others.

Longitudinal follow-up to near final height of auxological changes in girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analog and grouped by pretreatment body mass index level.

Purpose Reported changes in body mass index (BMI) in central precocious puberty (CPP) during and after gonadotropin-releasing hormone analog (GnRHa) treatment are inconsistent. We, therefore, investigated auxological parameters in GnRHa-treated girls with idiopathic CPP (ICPP) until attainment of near final height (NFH). Methods From the medical records of 59 ICPP girls who attained NFH after GnRHa therapy, auxological changes were compared between overweight (BMI≥85th percentile) and normal-weight (BMI<85th percentile) groups. BMIs were changed into standard deviation scores (BMISDSs) for subject chronologic age (BMISDS-CA) and bone age (BMISDS-BA).Results The incidence of overweight including obesity was high at the start of therapy (35.6%). The predicted adult height (PAH) at start of therapy was significantly shorter than the midparental height (MPH), whereas PAH at end of therapy approached MPH, and NFH was greater than MPH. Height velocity (HV) in the overweight group was higher during GnRHa therapy than that in the normal-weight group, but those in the two groups were not different after therapy until NFH. Both BMISDS-CA and BMISDS-BA increased significantly during therapy, but both BMISDSs decreased significantly after therapy until NFH. At NFH, neither BMISDS was different from that at baseline. In the normal-weight group, both BMISDSs increased during therapy and were maintained until NFH. In the overweight group, neither BMISDS changed during therapy, but there was a decrease after therapy until NFH.Conclusions The different patterns of BMISDS change during and after GnRHa therapy until NFH between the 2 groups were related to the different HV during GnRHa therapy.

Clinical Case Seminar: Postmenopausal androgen excess-challenges in diagnostic work-up and management of ovarian thecosis.

Postmenopausal hyperandrogenism can be tumour- or non-tumour-related, with pathology residing either in the ovary or adrenal gland(s). The tempo of investigation is determined by the clinical severity of hyperandrogenism (presence/absence of actual virilisation) and degree of serum testosterone elevation. When clinical or biochemical hyperandrogenism is severe, rapidly developing, or associated with hypercortisolism, screening for adrenocortical or ovarian carcinoma with cross-sectional imaging should be prioritised over detailed biochemical evaluation. Adrenal hyperandrogenism is readily characterised, both biochemically and radiologically. By contrast, even a combination of high-resolution imaging with laboratory evaluation, including dynamic endocrine testing, often cannot distinguish between ovarian hyperthecosis (OH) and virilising ovarian tumour (VOT); a definitive diagnosis usually emerging only after histological examination of excised ovaries. VOTs are typically below the resolution-limit of current imaging modalities and exhibit suppression of gonadotropin-dependent androgen secretion with GnRH-analogue therapy. Thus, for well-characterised ovarian hyperandrogenism, laparoscopic bilateral salpingo-oophorectomy may serve both as a diagnostic and therapeutic procedure. Nevertheless, women unable or unwilling to undergo ovarian surgery can be reassured that malignant VOTs are exceedingly rare and that long-term medical therapy with oral antiandrogens or GnRH-analogues is safe and well-tolerated. OH is strongly associated with insulin-resistance, with hyperinsulinaemia acting synergistically with raised gonadotropin levels to stimulate thecal cell hyperplasia and androgen secretion by the postmenopausal ovary, which lacks granulosa cell aromatase activity and thus cannot convert testosterone to 17 beta estradiol. Thus, features of metabolic syndrome may indicate OH, and significant reductions in androgens can thereby potentially be achieved with lifestyle measures and/or insulin-sensitising drugs.

Final height and intrauterine growth retardation

Approximately 10% of small for gestational age (SGA) children maintain a small body size throughout childhood and often into adult life with a decreased pubertal spurt. Growth hormone (GH) therapy increases short-term growth in a dose–dependent manner and adult height had now been well documented. Shorter children might benefit from a higher dose at start (50μg/kg/day). The response to GH treatment was similar for both preterm and term short SGA groups and the effect of GH treatment on adult height showed a wide variation in growth response. As a whole, mean adult height is higher than −2 SDS in 60% of patients and 70% reached an adult height in their target height with better results with higher doses and combined GnRH analog therapy in those who were short at onset of puberty.

Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues

Background/Aims: Gonadotropin-releasing hormone analogues (GnRHa) represent the gold standard treatment for central precocious puberty (CPP). We aimed to assess the effects of GnRHa treatment on metabolic outcomes, bone status, and polycystic ovary syndrome (PCOS) prevalence in young girls with idiopathic CPP (ICPP). Methods: We enrolled 94 ICPP girls who were at least 2 years after menarche and had already attained adult height at the time of the study: 56 previously treated with depot triptorelin (3.4 ± 0.6 years) and 38 untreated. Auxological parameters, lipid profile, homeostatic model assessment of insulin resistance (HOMA-IR), bone state, and prevalence of PCOS were assessed. Results: The 2 groups were similar for body mass index (BMI) and waist circumference. HOMA-IR, dehydroepi­androsterone sulfate, and Δ4-androstenedione were higher in the treated than in the untreated subjects (p < 0.001). Significant differences were found for amplitude-dependent speed of sound (p < 0.03) and bone transmission time z-scores (p < 0.01). The prevalence of PCOS was higher in the treated than in the untreated subjects (p < 0.04). Conclusion: GnRHa therapy is associated with hyperandrogenism and an increase in insulin resistance and PCOS prevalence, but not with increased BMI or lipid profile alterations. Long-term evaluations at the time of expected peak bone mass achievement are needed to understand the persistent or transient nature of subtle bone abnormalities.

Effects of pomegranate extract in supplementing gonadotropin-releasing hormone therapy on idiopathic central precocious puberty in Chinese girls: a randomized, placebo-controlled, double-blind clinical trial.

Central precocious puberty (CPP) without organic abnormality is called idiopathic CPP (ICPP). The objective of this trial was to evaluate the effects of pomegranate extract in supplementing gonadotropin-releasing hormone (GnRH) analog therapy on ICPP-affected girls in the Chinese population. 286 girls, diagnosed with ICPP were initially enrolled into this trial, and among them 225 eligible patients were randomized to receive a combinational GnRH analog treatment supplemented with either a placebo or pomegranate extract on a daily basis for a period of 3 months. Their demographics, secondary sexual characteristics and hormone profiles were analyzed at baseline and end of trial. After 3 months of treatment, demographic profiles including bone age, growth velocity and height standard deviation score for bone age, and secondary sexual characteristics including uterus and ovary volume, as well as serum hormone profiles including estradiol, peak luteinizing hormone and insulin-like growth factor 1 were all significantly improved in girls receiving a combinational treatment of both GnRH analog and pomegranate extract. Daily consumption of pomegranate extract was able to supplement and improve the treatment outcomes of the GnRH analog therapy for ICPP in Chinese girls.

Changes in Body Mass Index in Girls with Idiopathic Central Precocious Puberty under Gonadotropin-Releasing Hormone Analogue Therapy: The Spanish Registry

Background: The influence of gonadotropin-releasing hormone analogue (GnRHa) treatment on body mass index (BMI) evolution in girls with idiopathic central precocious puberty (CPP) is unclear. Hence, we aimed to evaluate the effect of GnRHa treatment on BMI-standard deviation score (SDS) from diagnosis of idiopathic CPP until adult height. Methods: An observational study of girls diagnosed with CPP in Spain was carried out between January 2008 and December 2014. A computer program was designed to process clinical and biological data from patients treated in 55 departments of pediatric endocrinology throughout the country. The inclusion criteria were (1) girls diagnosed with CPP before 8 years of age; (2) born after 1992; (3) with a difference between bone and chronological age of at least 1 year, and (4) with a luteinizing hormone peak >7 U/l during luteinizing hormone-releasing hormone testing. The influence of GnRHa treatment on BMI-SDS evolution was analyzed. Results: Data from 333 girls (22.2% adopted) were evaluated. We report follow-up data at 6, 12, 24, 36, 48 and 60 months and adult height from 269, 232, 198, 153, 105, 56 and 49 girls, respectively. During treatment, there was an increase in BMI-SDS of 0.43 ± 1.17 (95% CI: 0.20-0.64). At adult height (n = 49), BMI-SDS was 1.51 ± 1.38, which was 0.60 ± 1.09 higher than at diagnosis (95% CI: 0.43-0.75). Conclusions: During treatment with GnRHa, girls experience a significant increase in BMI-SDS that persists after therapy is stopped and adult height has been reached.

Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies.

IntroductionAndrogen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to “castrate” levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate (LA), a GnRH agonist that has previously demonstrated efficacy in testosterone suppression to <50 ng/dL in patients on ADT. This analysis investigates the ability of these LA formulations to suppress to ≤20 ng/dL levels.MethodsIn two of five AbbVie/Abbott clinical trials of microsphere formulations of LA for ADT, analytic technology permitting testosterone detection as low as 3 ng/dL was used and thus was selected for this analysis. Both trials were open-label, fixed-dose studies in prostate cancer patients, naïve to ADT. Patients received either 30 mg (4-month formulation; n=49) or 45 mg (6-month formulation; n=151) depot injections of LA microspheres. Treatment duration was up to 32 weeks for the 4-month formulation and 48 weeks for the 6-month formulation. The proportion of patients achieving the 20 ng/dL threshold was determined every 4 weeks.ResultsPooled analysis showed that 152 of 193 (79%) of patients achieved serum testosterone levels of ≤20 ng/dL at 4 weeks, and sustained the improvement at week 24 (169/189, 89%). Additionally, in the 6-month study, 127/135 (94.1%) patients were suppressed to ≤20 ng/dL at 48 weeks.ConclusionBoth 4- and 6-month intramuscular depot formulations of LA achieved and maintained mean serum testosterone levels ≤20 ng/dL in the vast majority of patients as early as 4 weeks following treatment initiation. Additional research on the clinical relevance of this lower testosterone threshold is warranted.

Effects and safety of combination therapy with gonadotropin-releasing hormone analogue and growth hormone in girls with idiopathic central precocious puberty: a meta-analysis.

This meta-analysis is to evaluate the effects and safety of the combination therapy for girls with idiopathic central precocious puberty (ICPP). Electronic databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that adopted gonadotropin-releasing hormone analogue (GnRHa) therapy and GnRHa plus growth hormone (GH) combination therapy to treat ICPP girls. A total of six RCTs (162 patients) and six CCTs (247 patients) were included. Compared to the GnRHa therapy group, the combination therapy group achieved taller final height (mean difference, MD=2.81cm, 95% CI 1.76-3.87, four CCTs; MD=4.30cm, 95% CI 0.59-8.01, one RCT); greater progression of final height compared with target height (MD=3.92cm, 95% CI 3.12-4.73, four CCTs; MD=4.00cm, 95% CI 1.93-6.07, One RCT) and larger height gains (MD=3.49cm, 95% CI 0.97-6.01, four CCTs; MD=3.88cm, 95% CI 0.15-7.61, one RCT). No severe adverse effects of treatment were reported. For ICPP girls, the GnRHa and GH combination therapy had advantages over GnRHa alone on final height and no severe adverse effects were reported. We recommend comprehensive assessment of the individual growth rate, patient compliance, the clinical effects, the height expectations of individual patients and the treatment cost to the family in order to identify the best therapy for individual patients.

Combined surgical and medical management for recurrent cellular angiofibroma of vulva in a young female - a case report

&lt;p class="abstract"&gt;&lt;span lang="EN-US"&gt;Cellular angiofibroma of the vulva is a benign tumor of mesenchymal origin in female and male genital tract composed of stromal spindle cells and mixture of adipose tissue, prominently vascular in nature. Here we present a case of recurrent cellular angiofibroma in a 27 years old young woman which was the 5th time recurrence when she presented to us. Diagnosis was confirmed by MRI, histopathology study and immunohistochemistry. With wide excision of tumor followed by GnRH analogue therapy post operatively, she is now tumour free even after 20 months of surgery.&lt;/span&gt;&lt;/p&gt;

A Rare Case of Nocturnal Urinary Incontinence and Menuria after Lower Segment Cesarean Section

ABSTRACT Misgav Ladach technique for lower segment cesarean section (LSCS) is considered advantageous universally, but debate still continues about nonclosure in layers and further consequences; hence, careful selection of cases and intraoperative decision of closure in layers is important. The classical Youssef's syndrome comprises cyclic hematuria, amenorrhea, menuria, and complete urinary continence in a patient who had LSCS. Hereby, we present a case report of a woman who suffered with chronic pelvic pain, menuria, and nocturnal eneuresis after her LSCS for obstructed labor, although not exactly the same as Youssef syndrome but rare in occurrence and relieved after adhesiolysis and gonadotropin-releasing hormone (GnRH) analog therapy. How to cite this article Chaudhry P, Shrivastava DS, Bhute S, Jajoo S. A Rare Case of Nocturnal Urinary Incontinence and Menuria after Lower Segment Cesarean Section. J Med Sci 2016;2(1):23-25.

Body image and depression in girls with idiopathic precocious puberty treated with gonadotropin-releasing hormone analogue.

PurposePrecocious puberty (PP) is associated with psychological and behavioral problems. This study aimed to evaluate the perception of body image and depression in girls with PP receiving gonadotropin-releasing hormone (GnRH) analogue therapy.MethodsFrom March to August 2013, 82 girls with PP receiving GnRH analogue therapy were enrolled. Height, weight, body mass index, and stages of pubertal development were assessed. Participants completed a series of questionnaires on their body image perception and pubertal self-assessment. The depression score was calculated using the Korean Kovacs' Children's Depression Inventory.ResultsThe patients perceived their body to be more obese than the controls did. The mean depression score did not differ between the patients and controls. The mean depression scores according to Tanner stages (1: prepubertal, 2: early pubertal, and 3–5: mid to late pubertal stage) by self-assessment were 5.2±3.6, 6.8±4.9, and 11.4±10.1 (P<0.05), respectively. The perception of overall body build and figure (%) and the mean depression scores in patients were: dissatisfied (25.6%, 9.7±7.8) and satisfied (74.4%, 5.5±3.4) (P<0.05). In multiple linear regression analysis, self-T3 (Tanner stage 3–5 by self-awareness) and dissatisfaction about overall body build and figure were found to significantly affect the depression score(P<0.05).ConclusionThe perception of pubertal status and satisfaction about height or weight are unrelated to objective physical findings. Patients with PP are prone to distorted perception about their body image and breast development. Such incorrect body image seems to contribute to depression score.

Influence of Different Regimens of Prostate Cancer Androgen Deprivation on Metabolic Syndrome and Sexual Dysfunction

Androgen deprivation remains a golden standard therapy in advance Prostate cancer. Besides adequate suppression of the tumor growth, ADT causes temporary or even permanent sexual dysfunction along with the high risk of metabolic complications. In our prospective study we have included 56 patients with advanced forms of prostrate cancer and remained sexual activity whom were subjects to different regimens of ADT. The primary goal of our study was evaluation of the degree of metabolic complications and time to regain sexual activity using continuous and intermittent GnRH analogues therapy and sequential therapy with GnRH analogues and bicalutamide.

Central Precocious Puberty: Adult Height in Girls Treated with Quarterly or Monthly Gonadotropin-Releasing Hormone Analog Triptorelin

Background/Aims: Treatment with quarterly gonadotropin-releasing hormone (GnRH) analogs may improve compliance and optimize outcome in girls with central precocious puberty (CPP), but long-term comparative data between the new and the monthly formulations are very scarce. Methods: A group of girls with idiopathic CPP (n = 13; age 7.9 ± 0.6 years) were treated from the beginning with quarterly triptorelin (11.25 mg/90 days) and followed up to the achievement of adult height (AH). A group of girls with idiopathic CPP (n = 12; age 8.0 ± 0.6 years) treated with monthly triptorelin (3.75 mg/28 days) served as controls. Results: The AH (157.1 ± 4.9 cm) of girls treated with quarterly triptorelin was not significantly different from their mid-parental height (159.7 ± 3.8 cm) and significantly increased in comparison with predicted AH (average tables) at the beginning of GnRH analog therapy. The AH of girls treated with quarterly triptorelin was not significantly different in comparison with that of girls treated with the monthly formulation (158.1 ± 6.6 cm; mid-parental height 158.4 ± 5.0 cm). Conclusion: Treatment with quarterly triptorelin formulation permitted to achieve an AH adequate for mid-parental height in girls with CPP. Significant differences of AH between girls with CPP treated with quarterly or monthly formulations were not found.

Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones

To determine the effect of GnRH analogues (GnRH-a) leuprolide acetate (LA) and cetrorelix acetate on gonadal hormone-regulated expression of extracellular matrix in uterine leiomyoma three-dimensional (3D) cultures. Laboratory study. University research laboratory. Women undergoing hysterectomy for symptomatic leiomyomas. The 3D cell cultures, protein analysis, Western blot, immunohistochemistry. Expression of extracellular matrix proteins, collagen 1, fibronectin, and versican in leiomyoma cells 3D cultures exposed to E2, P, LA, cetrorelix acetate, and combinations for 24- and 72-hour time points. The 3D leiomyoma cultures exposed to E2 for 24 hours demonstrated an increased expression of collagen-1 and fibronectin, which was maintained for up to 72 hours, a time point at which versican was up-regulated significantly. Although P up-regulated collagen-1 protein (1.29 ± 0.04) within 24 hours of exposure, significant increase in all extracellular matrix (ECM) proteins was observed when the gonadal hormones were used concomitantly. Significant decrease in the amount of ECM proteins was observed on use of GnRH-a, LA and cetrorelix, with 24-hour exposure. Both the compounds also significantly decreased ECM protein concentration despite the presence of E2 or both gonadal hormones. This study demonstrates that GnRH-a directly affect the gonadal hormone-regulated collagen-1, fibronectin, and versican production in their presence. These findings suggest that localized therapy with GnRH-a may inhibit leiomyoma growth even in the presence of endogenous gonadal hormone exposure, thereby providing a mechanism to eliminate the hypoestrogenic side effects associated with GnRH-a therapy.

The Influence of GnRH Analog Therapy on Growth in Central Precocious Puberty.

Children with central precocious puberty (CPP) present various somatic and psychological abnormalities. The aim of the study was to evaluate growth changes in girls with central precocious puberty treated with GnRH analog therapy and to analyze the factors affecting the auxological response to this treatment. The study group consisted of 40 girls with puberty onset aged 6.0 ± 1.9 years (mean, ± SD), treated with 3.75 mg decapeptyl depot intramuscularly every 28 days. The treatment was initiated at the age of 7.5 ± 2.2 years and continued for 3.3 ± 2.3 years, until the age of 11.4 ± 0.9 years. Height (Ht), height standard deviation score (HtSDS), statural age, bone age and Ht prediction. During the treatment a decline in HtSDS from 2.0 ± 1.36 to 1.24 ± 1.0 was observed (p = 0.0002); and a deceleration in the maturation of bones of 1.0 ± 0.29 year in the first year and 0.66 ± 0.33 year in the following years (p = 0.0008). The HtSDS at the end of the treatment was significantly higher than was predicted in pretreatment (1.33 ± 1.04 vs. 0.07 ± 1.39, p = 0.0005). Ht and HtSDS after treatment were positively correlated with the predicted Ht (PAH) before treatment and negatively correlated with the bone age/statural age ratio before treatment (p < 0.05). The PAH before and after treatment correlated inversely with the bone age/statural age ratio (p < 0.05). Two subgroups were analyzed according to the patients' age when therapy was introduced: group 1 included girls who were under the age of 7 when therapy was introduced, and group 2 included girls aged 7 or older. There was a statistically significant difference in the PAH SDS before treatment between these two subgroups: Group I (-) 1.3 ± 1.8 vs. Group II (-) 0.14 ± 1.2 and there was no difference in the PAH SDS after treatment: Group I (-) 0.7 ± 1.1 vs. Group II 0.31 ± 1.2. The child's age at the beginning of GnRHa therapy was an important predictor of height prognosis; the therapy introduced under the age of 7 improves the PAH during treatment. Height prediction during the entire treatment period is worse in children with more advanced bone age for their statural age at the onset of treatment.

Long term outcome of gonadotrophin releasing hormone analogue therapy in Sri Lankan children with central precocious puberty

Introduction: Central precocious puberty (CPP) needs treatment to minimise the psychosocial impact and optimize the auxological outcome. Objective: To analyse the growth pattern and outcome of gonadotrophin releasing hormone analogue (GnRHa) therapy in a cohort of children with CPP Method: Heights were serially recorded, skeletal age monitored and height velocities calculated in children with CPP prospectively followed up from presentation to cessation of therapy with GnRHa. The response to treatment was assessed as the height standard deviation scores (SDS), ratio of chronological age to bone age and reduction of height velocity with treatment and the significance was determined using the paired ‘t’ test and ANOVA. Their heights when last seen were compared with their predicted mature heights and target heights which were calculated based on the bone age prior to treatment and the parents’ heights respectively. Results: There were 9 patients (8 girls) with a mean age of 56.4 (19.1) and 124.2 (15.2) months at onset and completion of treatment respectively. There was a significant reduction in the height SDS, bone age acceleration and height velocity with treatment. The heights at final assessment were acceptable for the national average in the majority. Conclusion: There was a significant reduction in the height SDS, bone age acceleration and height velocity in the cohort of children with CPP treated with a GnRHa. Sri Lanka Journal of Child Health 2015; 44 (2): 82-87

A randomised, double-blind study comparing the addition of bicalutamide with or without dutasteride to GnRH analogue therapy in men with non-metastatic castrate-resistant prostate cancer

BackgroundBicalutamide blocks androgen action and is frequently used in men with non-metastatic, castration-resistant prostate cancer (CRPC). By reducing intracellular dihydrotestosterone, dutasteride (dual 5-alpha reductase inhibitor) could increase the effectiveness of bicalutamide in this setting. The objective of the study is therefore to prospectively evaluate dutasteride plus bicalutamide in men with asymptomatic, non-metastatic CRPC with rising prostate-specific antigen (PSA). MethodsProstate cancer patients with rising PSA whilst on first-line androgen deprivation therapy (ADT) were randomised (1:1) in a double-blind trial to receive bicalutamide 50mg plus placebo or bicalutamide 50mg plus dutasteride 3.5mg once daily for 18months.Randomisation was stratified by centre; treatment assignments were generated using GlaxoSmithKline’s RandAll System. Subjects who completed 18months could participate in the 2-year extension. Central laboratory and study sites/monitors remained treatment-blinded.Primary end-point was time to disease progression (TDP) up to 42months (defined as PSA progression from baseline or nadir, radiographic disease progression, death from prostate cancer or receipt of rescue medication). FindingsThere was no statistically significant difference in TDP in 127 men treated with bicalutamide/dutasteride (n=62) compared with bicalutamide/placebo (n=65) (hazard ratio (HR)=0.94 [95% confidence interval (CI) 0.61, 1.46]; p=0.79). The estimated median TDP was 425days (95% CI 302, 858) in the bicalutamide/placebo group and 623days (95% CI 369, 730) in the bicalutamide/dutasteride group. There was no statistically significant difference between the treatment groups for any secondary efficacy end-points, including time to treatment failure or PSA response. In the multivariate analysis, age, non-White race, higher baseline testosterone and lower baseline PSA were associated with longer TDP. Adverse events were comparable between treatment groups. InterpretationIn men with non-metastatic CRPC, adding dutasteride to bicalutamide did not significantly prolong TDP. Prospective data are provided concerning the common practice of using bicalutamide in this setting.

Add-back therapy with GnRH analogues for uterine fibroids.

Add-back therapy with GnRH analogues for uterine fibroids.